全文获取类型
收费全文 | 135篇 |
免费 | 19篇 |
出版年
2023年 | 1篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 4篇 |
2013年 | 5篇 |
2012年 | 4篇 |
2011年 | 1篇 |
2010年 | 2篇 |
2009年 | 6篇 |
2008年 | 6篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 17篇 |
2004年 | 7篇 |
2003年 | 11篇 |
2002年 | 7篇 |
2001年 | 11篇 |
2000年 | 4篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1994年 | 4篇 |
1993年 | 10篇 |
1992年 | 1篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1955年 | 1篇 |
1951年 | 1篇 |
1949年 | 1篇 |
排序方式: 共有154条查询结果,搜索用时 31 毫秒
71.
Alison Tonks 《BMJ (Clinical research ed.)》2004,328(7434):293
72.
73.
The most prominent tyrosyl-phosphorylated protein in maturing sea star oocytes was identified as the 44 kDa myelin basic protein (MBP) kinase p44mpk. Immunoblotting studies with anti-phosphotyrosine PY-20 antibody and phosphoamino acid analysis of in vivo [32P]phosphate-labelled p44mpk showed that the tyrosyl phosphorylation of the kinase correlated with a greater than 10-fold stimulation of its MBP phosphotransferase activity. The activation of p44mpk was reversed almost completely by purified preparations of the protein-tyrosyl phosphatases CD45 and 1B. Purified p44mpk has previously been shown to undergo autophosphorylation in vitro on seryl residues and this was associated with further enhancement of its MBP phosphorylating activity (Sanghera et al. (1991) J. Biol. Chem. 266, 6700-6707). p44mpk also underwent seryl phosphorylation during oocyte maturation, and the protein-seryl/threonyl phosphatase 2A reversed partially the maturation-associated stimulation of its MBP kinase activity. The properties of p44mpk resemble the murine 42 kDa mitogen-activated protein kinase (p42mapk). While p44mpk may feature the phosphorylatable tyrosyl residue that is critical for activation in p42mapk, it lacks the upstream threonyl phosphorylation site that is also required for p42mapk activity (Payne et al. (1991) EMBO J: 10, 885-892). These findings indicate partial differences in the regulatory mechanisms that govern the activities of these isozymes. 相似文献
74.
75.
Gaofeng Fan Guang Lin Robert Lucito Nicholas K. Tonks 《The Journal of biological chemistry》2013,288(34):24923-24934
Ovarian cancer, which is the leading cause of death from gynecological malignancies, is a heterogeneous disease known to be associated with disruption of multiple signaling pathways. Nevertheless, little is known regarding the role of protein phosphatases in the signaling events that underlie the disease; such knowledge will be essential to gain a complete understanding of the etiology of the disease and how to treat it. We have demonstrated that protein-tyrosine phosphatase 1B (PTP1B) was underexpressed in a panel of ovarian carcinoma-derived cell lines, compared with immortalized human ovarian surface epithelial cell lines. Stable restoration of PTP1B in those cancer cell lines substantially decreased cell migration and invasion, as well as proliferation and anchorage-independent survival. Mechanistically, the pro-survival IGF-1R signaling pathway was attenuated upon ectopic expression of PTP1B. This was due to dephosphorylation by PTP1B of IGF-1R β-subunit and BRK/PTK6, an SRC-like protein-tyrosine kinase that physically and functionally interacts with the IGF-1R β-subunit. Restoration of PTP1B expression led to enhanced activation of BAD, one of the major pro-death members of the BCL-2 family, which triggered cell death through apoptosis. Conversely, inhibition of PTP1B with a small molecular inhibitor, MSI-1436, increased proliferation and migration of immortalized HOSE cell lines. These data reveal an important role for PTP1B as a negative regulator of BRK and IGF-1Rβ signaling in ovarian cancer cells. 相似文献
76.
Alison Tonks 《BMJ (Clinical research ed.)》2008,336(7637):186-188
77.
78.
Vanadate and molybdate increase tyrosine phosphorylation in a 50-kilodalton protein and stimulate secretion in electropermeabilized platelets 总被引:4,自引:0,他引:4
Addition of vanadate and molybdate to electropermeabilized human platelets caused a time- and dose-dependent increase in the phosphotyrosyl content of 50- and 38-kDa proteins. This effect can most likely be attributed to an inhibition of protein-tyrosine-phosphatase activity because vanadate and molybdate inhibited this activity in platelet extracts by greater than 97% while causing an increase in tyrosyl phosphorylation of artificial substrates that had been added to the same extracts. The addition of vanadate and molybdate to the electropermeabilized platelets also induced an increase in serotonin and PDGF secretion. Interestingly, the secretion of these components tightly correlated in a time- and dose-dependent fashion with the phosphorylation of the 50-kDa protein on tyrosyl residues. This suggests that the tyrosine phosphorylation of this protein may be closely linked to the platelet activation cascade. 相似文献
79.
80.
Ticknor LO Kolstø AB Hill KK Keim P Laker MT Tonks M Jackson PJ 《Applied and environmental microbiology》2001,67(10):4863-4873
We examined 154 Norwegian B. cereus and B. thuringiensis soil isolates (collected from five different locations), 8 B. cereus and 2 B. thuringiensis reference strains, and 2 Bacillus anthracis strains by using fluorescent amplified fragment length polymorphism (AFLP). We employed a novel fragment identification approach based on a hierarchical agglomerative clustering routine that identifies fragments in an automated fashion. No method is free of error, and we identified the major sources so that experiments can be designed to minimize its effect. Phylogenetic analysis of the fluorescent AFLP results reveals five genetic groups in these group 1 bacilli. The ATCC reference strains were restricted to two of the genetic groups, clearly not representative of the diversity in these bacteria. Both B. anthracis strains analyzed were closely related and affiliated with a B. cereus milk isolate (ATCC 4342) and a B. cereus human pathogenic strain (periodontitis). Across the entire study, pathogenic strains, including B. anthracis, were more closely related to one another than to the environmental isolates. Eight strains representing the five distinct phylogenetic clusters were further analyzed by comparison of their 16S rRNA gene sequences to confirm the phylogenetic status of these groups. This analysis was consistent with the AFLP analysis, although of much lower resolution. The innovation of automated genotype analysis by using a replicated and statistical approach to fragment identification will allow very large sample analyses in the future. 相似文献